Ertapenem (CAS Registry Number 153832-46-3; IUPAC Name: (4R,5S,6S)-3-[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid) is a carbapenem antibiotic by the structure:

Ertapenem is used to treat infectious bacteria, including gram positive and gram negative, aerobic and anaerobic bacteria.
WO 9857973 A1 discloses a process wherein ertapenem is obtained after the preparation of a monoprotected intermediate and subsequent deprotection via hydrogenation. In WO 9802439 A1 the preparation of a multiple protected intermediate of a carbapenem compound in an aprotic, polar solvent in the presence of a base is described. WO 2008062279 A2 discloses a process for the preparation of a diprotected, amorphous intermediate of ertapenem followed by deprotection and isolation of amorphous ertapenem. In WO 03026572 A2 a crystalline form A of the monosodium salt of ertapenem and its preparation by means of crystallization starting from a aqueous ertapenem solution and addition of organic solvents, pH value adjustment and addition of anti-solvents. IN 018900H2007 discloses the preparation of amorphous ertapenem starting from an aqueous ertapenem solution by pH value adjustment, addition of a precipitating agent and anti-solvents.
However, said prior art provides only processes having major drawbacks. For example, the diprotected intermediate obtained in WO 2008062279 A2 is not stable and requires a complicated isolation procedure, which leads to lower yields and the formation of byproducts.
Therefore, there is a constant search for new key intermediates, in particular for new intermediate suitable for the production of ertapenem or its salts, which are obtained, purified and optionally crystallized in a convenient way. Moreover, there is a constant search for new processes for the preparation of ertapenem or its salts.
Therefore, it was an object of the present invention to provide new key intermediates, in particular new intermediate suitable for the production of ertapenem or its salts, which may be obtained, purified and optionally crystallized in a convenient way.
It was a further object of the present invention to provide new key intermediates in crystalline form, in particular new intermediate suitable for the production of ertapenem or its salts, which may be obtained, purified and crystallized in a convenient way.
It was another object of the present invention to provide a process for the preparation of such key intermediates, in particular such intermediates suitable for the production of ertapenem or its salts.
It was another object of the present invention to provide a process for the preparation of such key intermediates in crystalline form, in particular such intermediates in crystalline form suitable for the production of ertapenem or its salts.
It was a further object of the present invention to provide a process for the preparation of such key intermediates, in particular such intermediates suitable for the production of ertapenem or its salts from known starting materials, e.g. the starting materials used in WO 2008062279 A2.
It was a further object of the present invention to provide a process for the preparation of such key intermediates in crystalline form, in particular such intermediates in crystalline form suitable for the production of ertapenem or its salts from known starting materials, e.g. the starting materials used in WO 2008062279 A2.
It was a further object of the present invention to provide an improved process for the preparation of ertapenem or its salts starting from known starting materials, e.g. the starting materials used in WO 2008062279 A2.
It was another object of the present invention to provide an improved process for the preparation of ertapenem or its salts starting from the new key intermediates.
It was a further object of the present invention to provide an improved process for the preparation of ertapenem or its salts starting from the new key intermediates in crystalline form.